Bhartiya Deepa
Stem Cell Biology Department, ICMR-National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, 400012, India.
Stem Cell Res Ther. 2021 Jan 21;12(1):73. doi: 10.1186/s13287-021-02142-x.
Life-long tissue homeostasis of adult tissues is supposedly maintained by the resident stem cells. These stem cells are quiescent in nature and rarely divide to self-renew and give rise to tissue-specific "progenitors" (lineage-restricted and tissue-committed) which divide rapidly and differentiate into tissue-specific cell types. However, it has proved difficult to isolate these quiescent stem cells as a physical entity. Recent single-cell RNAseq studies on several adult tissues including ovary, prostate, and cardiac tissues have not been able to detect stem cells. Thus, it has been postulated that adult cells dedifferentiate to stem-like state to ensure regeneration and can be defined as cells capable to replace lost cells through mitosis. This idea challenges basic paradigm of development biology regarding plasticity that a cell enters point of no return once it initiates differentiation. The underlying reason for this dilemma is that we are putting stem cells and somatic cells together while processing for various studies. Stem cells and adult mature cell types are distinct entities; stem cells are quiescent, small in size, and with minimal organelles whereas the mature cells are metabolically active and have multiple organelles lying in abundant cytoplasm. As a result, they do not pellet down together when centrifuged at 100-350g. At this speed, mature cells get collected but stem cells remain buoyant and can be pelleted by centrifuging at 1000g. Thus, inability to detect stem cells in recently published single-cell RNAseq studies is because the stem cells were unknowingly discarded while processing and were never subjected to RNAseq. This needs to be kept in mind before proposing to redefine adult stem cells.
成体组织的终身组织稳态据推测是由驻留干细胞维持的。这些干细胞本质上是静止的,很少分裂以自我更新并产生组织特异性的“祖细胞”(谱系受限且组织定向),后者迅速分裂并分化为组织特异性细胞类型。然而,事实证明,将这些静止的干细胞作为一个实体分离出来很困难。最近对包括卵巢、前列腺和心脏组织在内的几种成体组织进行的单细胞RNA测序研究未能检测到干细胞。因此,有人推测成体细胞去分化为干细胞样状态以确保再生,并且可以定义为能够通过有丝分裂替代丢失细胞的细胞。这一观点挑战了发育生物学中关于可塑性的基本范式,即细胞一旦开始分化就进入不可逆点。造成这种困境的根本原因是我们在进行各种研究时将干细胞和体细胞放在一起处理。干细胞和成体成熟细胞类型是不同的实体;干细胞是静止的,体积小,细胞器最少,而成熟细胞代谢活跃,有多个细胞器位于丰富的细胞质中。因此,当以100 - 350g离心时,它们不会一起沉淀下来。在这个速度下,成熟细胞被收集起来,但干细胞仍然漂浮,通过以1000g离心可以沉淀下来。因此,在最近发表的单细胞RNA测序研究中未能检测到干细胞,是因为在处理过程中干细胞被无意中丢弃了,从未进行RNA测序。在提议重新定义成体干细胞之前,需要牢记这一点。