by Amaris Castanon
For the
first time, scientists have generated haploid embryonic stem (ES) cell lines in
humans, as published in Nature. This could lead to novel cell
therapies for genetic diseases – even color blindness (Benvenisty et
al., 2016)
The study was performed by scientists from the Hebrew
University of Jerusalem(Israel) in
collaboration with Columbia University Medical
Center (CUMC)
and the New York Stem Cell Foundation (NYSCF).
The newly derived pluripotent, human ES cell lines
demonstrated their ability to ‘self-renew’ while maintaining a normal
haploid karyotype (i.e. without chromosomal breakdown after each generation) (Benvenisty et
al., 2016).
While gamete manipulation in other mammalian species
has yielded several ES cell lines (Yang,
H. et al., Leeb, M. & Wutz, A.), this is the first study to report human cells capable of cell division
with merely one copy of the parent’s cell genome (Benvenisty et
al., 2016).
The genetic match between the stem cells and the egg
donor may prove advantageous for cell-based therapies of genetic diseases such
as diabetes, Tay-Sachs disease and even color blindness (Elling et al., 2011).
—
Mammalian cells are considered diploid due to the fact
that two sets of chromosomes are inherited: 23 from the father and 23 from the
mother (a total of 46) (Wutz,
2014; Yang
H. et al., 2013). Haploid cells contain a single set of 23 chromosomes and arise only
as post-meiotic germ cells (egg and sperm) to ensure the right number of
chromosomes end up in the zygote (embryo) (Li et al., 2014; Elling et al., 2011).
Other studies performed in an effort to generate
ES cells from human egg cells reported generating solely diploid (46
chromosome) human stem cells, which is a problem (Leeb,
M. et al., 2012; Takahashi, S. et al.,
2014). This study, however, reported inducing cell
division in unfertilized human egg cells (Benvenisty et
al., 2016).
The DNA was labeled with a florescent dye prior to
isolating the haploid stem cells and scattering (the haploid cells or the
cells) among the larger pool of diploid cells. The DNA staining demonstrated
that the haploid cells retained their single set of chromosomes, while
differentiating to other cell types including nerve, heart, and pancreatic
cells demonstrates their ability to give rise to cells of different lineage (pluripotency) (Benvenisty et
al., 2016).
Indeed, the newly derived haploid ES cells
demonstrated pluripotent stem cell characteristics, such as self-renewal
capacity and a pluripotency-specific molecular signature (Benvenisty et
al., 2016).
In addition, the group of researchers successfully
demonstrated usage of their newly derived human ES cells as a platform for loss-of-function genetic
screening. Therefore, elucidating the genetic screening potential of
targeting only one of the two copies of a gene.
These findings may facilitate genetic analysis in the
future by allowing an ease of gene
editing in cancer research and regenerative medicine.
This is a significant finding in haploid cells, due to
the fact that detecting the biological effects of a single-copy mutation in a
diploid cell is difficult. The second copy does not contain the mutation and
therefore serves as a ‘backup’ set of genes, making it a challenge for precise
detection.
The newly derived haploid ES cells will provide
researchers with a valuable tool for improving our understanding of human
development and genetic diseases.
This study has provided
scientists with a new type of human stem cell that will play an important role
in human functional genomics and regenerative medicine.
References:
Derivation and differentiation of haploid human embryonic stem cells. Sagi I, Chia G, Golan-Lev T, Peretz M, Weissbein U, Sui L, Sauer MV,
Yanuka O, Egli D, Benvenisty N. Nature. 2016 Apr
7;532(7597):107-11.
Elling, U. et al. Forward and reverse genetics through derivation of
haploid mouse embryonic stem cells. Cell Stem Cell 9, 563–574 (2011).
Leeb, M. et al. Germline potential of parthenogenetic haploid mouse
embryonic stem cells. Development 139, 3301–3305 (2012)
Leeb, M. & Wutz, A. Derivation
of haploid embryonic stem cells from mouse embryos.Nature 479, 131–134 (2011)
Li, W. et al. Genetic modification and screening in rat using haploid
embryonic stem cells. Cell Stem Cell 14, 404–414 (2014).
Takahashi, S. et al. Induction of the G2/M transition stabilizes haploid
embryonic stem cells. Development 141, 3842–3847 (2014)
Wutz, A. Haploid mouse embryonic stem cells: rapid genetic screening and
germline transmission. Annu. Rev. Cell Dev. Biol. 30, 705–722 (2014).